Coordinate overexpression of interferon-α–induced genes in systemic lupus erythematosus

Authors

  • Kyriakos A. Kirou,

    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
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  • Christina Lee,

    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
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  • Sandhya George,

    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
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  • Kyriakos Louca,

    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
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  • Ioannis G. Papagiannis,

    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
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  • Margaret G. E. Peterson,

    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
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  • Ngoc Ly,

    1. Expression Diagnostics, Inc., South San Francisco, California
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    • Drs. Woodward, Fry, and Wohlgemuth and Mr. Ly, Ms Lau, and Mr. Prentice hold stock in Expression Diagnostics, Inc. and are listed as inventors on a patent application submitted by Expression Diagnostics, Inc. for the use of peripheral blood gene expression for diagnosis and monitoring of autoimmune diseases.

  • Robert N. Woodward,

    1. Expression Diagnostics, Inc., South San Francisco, California
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    • Drs. Woodward, Fry, and Wohlgemuth and Mr. Ly, Ms Lau, and Mr. Prentice hold stock in Expression Diagnostics, Inc. and are listed as inventors on a patent application submitted by Expression Diagnostics, Inc. for the use of peripheral blood gene expression for diagnosis and monitoring of autoimmune diseases.

  • Kirk E. Fry,

    1. Expression Diagnostics, Inc., South San Francisco, California
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    • Drs. Woodward, Fry, and Wohlgemuth and Mr. Ly, Ms Lau, and Mr. Prentice hold stock in Expression Diagnostics, Inc. and are listed as inventors on a patent application submitted by Expression Diagnostics, Inc. for the use of peripheral blood gene expression for diagnosis and monitoring of autoimmune diseases.

  • Anna Yin-Har Lau,

    1. Expression Diagnostics, Inc., South San Francisco, California
    Search for more papers by this author
    • Drs. Woodward, Fry, and Wohlgemuth and Mr. Ly, Ms Lau, and Mr. Prentice hold stock in Expression Diagnostics, Inc. and are listed as inventors on a patent application submitted by Expression Diagnostics, Inc. for the use of peripheral blood gene expression for diagnosis and monitoring of autoimmune diseases.

  • James G. Prentice,

    1. Expression Diagnostics, Inc., South San Francisco, California
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    • Drs. Woodward, Fry, and Wohlgemuth and Mr. Ly, Ms Lau, and Mr. Prentice hold stock in Expression Diagnostics, Inc. and are listed as inventors on a patent application submitted by Expression Diagnostics, Inc. for the use of peripheral blood gene expression for diagnosis and monitoring of autoimmune diseases.

  • Jay G. Wohlgemuth,

    1. Expression Diagnostics, Inc., South San Francisco, California
    Search for more papers by this author
    • Drs. Woodward, Fry, and Wohlgemuth and Mr. Ly, Ms Lau, and Mr. Prentice hold stock in Expression Diagnostics, Inc. and are listed as inventors on a patent application submitted by Expression Diagnostics, Inc. for the use of peripheral blood gene expression for diagnosis and monitoring of autoimmune diseases.

  • Mary K. Crow

    Corresponding author
    1. Hospital for Special Surgery, and Weill Medical College of Cornell University, New York, New York
    • Department of Medicine, Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021
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    • Dr. Crow serves on the Scientific Advisory Board of, and holds stock options in, Expression Diagnostics, Inc.


Abstract

Objective

To study the contribution of interferon-α (IFNα) and IFNγ to the IFN gene expression signature that has been observed in microarray screens of peripheral blood mononuclear cells (PBMCs) from patients with systemic lupus erythematosus (SLE).

Methods

Quantitative real-time polymerase chain reaction analysis of healthy control PBMCs was used to determine the relative induction of a panel of IFN-inducible genes (IFIGs) by IFNα and IFNγ. PBMCs from 77 SLE patients were compared with those from 22 disease controls and 28 healthy donors for expression of IFIGs.

Results

Expression of IFNα-inducible genes was significantly higher in SLE PBMCs than in those from disease controls or healthy donors. The level of expression of all IFIGs in PBMCs from SLE patients with IFNα pathway activation correlated highly with the inherent responsiveness of those genes to IFNα, suggesting coordinate activation of that cytokine pathway. Expression of genes preferentially induced by IFNγ was not significantly increased in SLE PBMCs compared with control PBMCs. IFNα-regulated gene-inducing activity was detected in some SLE plasma samples.

Conclusion

The coordinate activation of IFNα-induced genes is a characteristic of PBMCs from many SLE patients, supporting the hypothesis that IFNα is the predominant stimulus for IFIG expression in lupus.

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